Hepatitis C virus (HCV) is a hepatotropic, plus (+) strand RNA virus that presents a major threat to human health, infecting an estimated 170 million people worldwide. Acute HCV infection often leads to persistent infection, resulting in damage to the liver. Typical forms of liver damage caused by HCV include cirrhosis, chronic hepatitis and liver carcinoma. Less than 50% of patients respond to the current standard treatment, which is alpha interferon, alone or in combination with ribavirin. Accordingly, there has been intense interest in developing more efficacious anti-HCV drugs. It has been shown that the 5′-nontranslated region (5′-NTR) of the +RNA contains an internal ribosome entry site (IRES), which directs cap-independent initiation of virus translation. Furthermore, certain portions of the IRES element are essential for the HCV replication process. The IRES would appear to be a good target for antiviral compounds. Detailed descriptions of the HCV IRES and its functions have been presented, e.g. by Honda et al., in Journal of Virology, 73(2), 1165-74 (1999) (incorporated herein by reference, especially page 1166, Materials and Methods), and Kim, et al. in Biochem. Biophys. Res. Commun., 290, 105-112, (2002).
The activity of putative HCV IRES binding molecules can be measured using an HCV replicon per, e.g., the teaching of Lohmann et al. in Science, 285, 110-113 (1999) (incorporated herein by reference, especially page 111, FIG. 1 and legend thereof) and Yi, et al. in Virology, 304, 197-210 (2002).
Given the high infection rate of HCV worldwide, and given the relatively low efficacy of the standard therapeutic methods, there is a need for anti-HCV compounds, e.g. for use in HCV assays and anti-HCV prophylactic and therapeutic applications.